1. Reproduction-Related Disorders
Part 3

2. Infertility
Infertility is defined as the inability to conceive after 1 year of unprotected intercourse.
It has been estimated that 93% of healthy couples practicing unprotected intercourse should expect to conceive within 1 year, and 100% will be successful within 2 years.
Primary infertility refers to couples or patients who have had no previous successful pregnancies.
Secondary infertility encompasses patients who have previously conceived, but are currently unable to conceive.

3. Infertility
Infertility problems often arise as a result of hormonal dysfunction of the hypothalamic- pituitary-gonadal axis.
Measurements of peptide and steroid hormones in the serum are therefore essential aspects of the evaluation of infertility, and are the focus of this section.

4. Male Infertility
A list of the most common male infertility factors is given in the table.
Laboratory evaluation of male infertility should begin with evaluation of semen, which should be followed by evaluation of endocrine parameters.

5. Male Infertility Factors
Endocrine Disorders
Hypothalamic dysfunction (Kallmann syndrome)
Pituitary failure (tumor, radiation,…)
Hyperprolactinemia (drug, tumor)
Exogenous androgens
Thyroid disorders
Adrenal hyperplasia
Testicular failure
Anatomic
Congenital absence of vas deferens
Obstructed vas deferens
Congenital abnormalities of ejaculatory system
Varicocele
Retrograde ejaculation
Abnormal Spermatogenesis
Unexplained azoospermia
Chromosomal abnormalities
Mumps orchitis
Cryptorchidism
Chemical or radiation exposure
Abnormal Motility
Absent cilia (Kartagener syndrome)
Antibody formation
Psychosocial
Unexplained impotence
Decreased libido

6. Male Infertility Evaluation of Semen
Semen analysis measures:
Semen should be analyzed within 1 hour after collection.
Although this assay reveals useful information for the initial evaluation of the infertile male, it is not a test of fertility.
It provides no insights into the functional potential of the spermatozoon to fertilize an ovum or to undergo the subsequent maturation processes required to achieve fertilization.
It is important to understand that while the results may correlate with “fertility,” the assay is not a direct measure of fertility
Ejaculate volume pH
Forward progression
Sperm count
Motility
Morphology

7. Male Infertility Evaluation of Semen
If semen analysis is abnormal, it should be repeated in ≈6 weeks.
Additional investigations may include measurement of sperm protein SP-10 via immunoassay.
SP-10 is testis-specific, arises within the acrosomal vesicle during spermatogenesis, and is associated with the acrosomal membranes and matrix of mature sperm.
A version of the test is available to check the success of vasectomy.

8. Male Infertility Evaluation of Obstruction
Obstruction of the male reproductive tract results in male infertility, and analysis of specific semen parameters has proved a useful adjunct to physical examination in the evaluation of male reproductive tract obstruction.
Testosterone produced after administration of hCG causes the (1) seminal vesicles, (2) epididymis, and (3) prostate to increase the volume of ejaculate.
An appropriate increase in serum testosterone without change in the ejaculate volume may indicate mechanical blockage.
Epididymis is a tube that connects a testicle to a vas deferens 

9. Male Infertility Evaluation of Endocrine Parameters
If severe oligospermia (low sperm count) or azoospermia (no measurable sperm in semen) is found, then measurement of (1) serum testosterone, (2) LH, & (3) FSH concentrations is necessary, with or without measurement of (4) prolactin and (5) TSH concentrations.
Hyperprolactinemia is a cause of secondary testicular dysfunction.
If hyperprolactinemia is found, it is vital to check for hypothyroidism, because elevated TRH concentrations result in hyperprolactinemia.
Thyrotropin-releasing hormone (TRH) Prolactin production can be stimulated by the hypothalamic peptides, thyrotropin-releasing hormone

10. Male Infertility Evaluation of Endocrine Parameters
Pituitary adenomas and drugs, such as antihypertensives, histamine H2 receptor antagonists also increase serum prolactin.
Hyperthyroidism and hypothyroidism will alter spermatogenesis.
Hyperthyroidism affects both pituitary and testicular function with alterations in the secretion of releasing hormones and increased conversion of androgens to estrogens.

11. Male Infertility Evaluation of Endocrine Parameters
Patients with borderline or suppressed testosterone conc. are evaluated with an hCG stimulation test.
With this test, an injection of 5000 IU hCG is administered intramuscularly following collection of a basal, early morning testosterone sample.
Serum testosterone is measured 72 hours later.
Hypogonadal men show a depressed rise in testosterone concentration in response to this challenge.
Doubling of testosterone concentration over baseline is consistent with normal Leydig cell function.
Failure to increase testosterone concentrations to greater than 150 ng/dL indicates primary hypogonadism.

13. Male Infertility Evaluation of Endocrine Parameters
Hypergonadotropic Hypogonadism
Measurement of the concentration of FSH is indicated in men with sperm count lower than 5 to 10 million/mL.
Elevated concentrations of FSH indicate:
Sertoli cell dysfunction and, in azoospermic men, (2) primary germinal cell failure, (3) Sertoli cell–only syndrome (a condition resulting in sterility due to the absence of living sperm cells in the semen), or (4) genetic conditions, such as Klinefelter syndrome (47,XXY karyotype).
Elevated FSH (>120 mIU/mL) in the setting of decreased testosterone (<200 ng/dL) and oligospermia indicate primary testicular failure.
Because its main function is to nourish the developing sperm cells through the stages of spermatogenesis, the Sertoli cell has also been called the "mother" or "nurse" cell.
Sertoli cells secrete inhibin and activins  — secreted after puberty, and work together to regulate FSH secretion
FSH Adult male: 1.5 to 12.4 mIU/ml; Test. Avg. Adult Male: 270 – 1070 ng/dL

14. Male Infertility Evaluation of Endocrine Parameters
Hypogonadotropic Hypogonadism
Decreased concentrations of testosterone (<200 ng/dL) and decreased concentrations of FSH (<10 mIU/mL) are suggestive of hypogonadotropic hypogonadism.
Administering GnRH may help to distinguish between gonadal insufficiencies caused by pituitary versus hypothalamic dysfunction.
One approach to this test involves the intravenous injection of 100 µg of GnRH with measurement of FSH and LH concentrations at 0, 30, 60, 120, and 180 minutes after injection.

15. Male Infertility Evaluation of Endocrine Parameters
An increase in serum gonadotropins of 10 mIU/mL or more over baseline is normal.
If little to no increase in gonadotropins is seen, pituitary disease is likely.
Patients with hypothalamic disease demonstrate a delayed but significant increase of 7 mIU/mL or more within 180 minutes.

16. Female Infertility
luteal phase defect, that lining doesn't grow properly each month. This can make it difficult to become or remain pregnant.

17. Female Infertility Evaluation of Female Infertility
The initial evaluation of female infertility includes a detailed history and physical examination.
The physical examination should include evaluation of:
The external genitalia and hair pattern (for signs of androgen excess including cliteromegaly, hirsutism, and virilization),
The pelvis (for masses, nodularity or tenderness),
The breasts (for signs of galactorrhea),
Neurological findings (sense of smell and visual impairments),
The thyroid (for enlargement or nodules), and
Body mass index.
the development of male physical characteristics (such as muscle bulk, body hair, and deep voice) in a female

18. Female Infertility Evaluation of Female Infertility
All abnormalities in the history and physical examination should be tracked.
A thorough medical and surgical history is also necessary including an assessment of:
The patient’s gravidity and parity,
Coital frequency,
Duration of infertility, and
Prior work up and treatment for infertility.
Also,
History of sexually transmitted infections,
Assessment of previous cervical cytologic and HPV testing and treatment, and
A menstrual history should be obtained.

19. Female Infertility Evaluation of Female Infertility
Concentrations of (1) TSH, (2) testosterone, and (3) prolactin should be measured if menstrual cycles are absent or irregular or if there are signs of galactorrhoea or thyroid abnormalities.
Ovulation reserve testing as discussed below should be considered in cases where diminished ovarian reserve is suspected.